|
1000
|
Abstract/Summary
|
-
<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>Transforming Growth Factor-β<jats:sub>1</jats:sub> (TGF-β<jats:sub>1</jats:sub>) is a genetic modifier in patients with cystic fibrosis (CF). Several single nucleotide polymorphisms (SNPs) of TGF-β<jats:sub>1</jats:sub> are associated with neutrophilic inflammation, lung fibrosis and loss of pulmonary function.</jats:p>
</jats:sec><jats:sec>
<jats:title>Aim</jats:title>
<jats:p>The aim of this study was to assess the relationship between genetic TGF-β<jats:sub>1</jats:sub> polymorphisms and pulmonary disease progression in CF patients. Furthermore, the effect of TGF-β<jats:sub>1</jats:sub> polymorphisms on inflammatory cytokines in sputum was investigated.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>56 CF-patients and 62 controls were genotyped for three relevant SNPs in their TGF-β<jats:sub>1</jats:sub> sequence using the SNaPshot® technique. Individual “slopes” in forced expiratory volume in 1 s (FEV<jats:sub>1</jats:sub>) for all patients were calculated by using documented lung function values of the previous five years. The status of <jats:italic>Pseudomonas aeruginosa (Pa)</jats:italic> infection was determined. Sputum concentrations of the protease elastase, the serine protease inhibitor elafin and the cytokines IL-1β, IL-8, IL-6, TNF-α were measured after a standardized sputum induction and processing.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>The homozygous TT genotype at codon 10 was associated with a lower rate of chronic <jats:italic>Pa</jats:italic> infection (<jats:italic>p</jats:italic> < 0.05). The heterozygous GC genotype at codon 25 was associated with lower lung function decline (<jats:italic>p</jats:italic> < 0.05). Patients with homozygous TT genotype at the promotor SNP showed higher levels of TNF-α (<jats:italic>p</jats:italic> < 0,05). Higher levels of TGF-β<jats:sub>1</jats:sub> in plasma were associated with a more rapid FEV<jats:sub>1</jats:sub> decline over five years (<jats:italic>p</jats:italic> < 0.05).</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>Our results suggest that polymorphisms in the TGF-β<jats:sub>1</jats:sub> gene have an effect on lung function decline, <jats:italic>Pa</jats:italic> infection as well as levels of inflammatory cytokines. Genotyping these polymorphisms could potentially be used to identify CF patients with higher risk of disease progression. TGF-β<jats:sub>1</jats:sub> inhibition could potentially be developed as a new therapeutic option to modulate CF lung disease.</jats:p>
</jats:sec>
|
|
1000
|
Hinweis
|
-
DeepGreen-ID: ad0ec4a980b6426d8407d545cb919664 ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
|
